Mechanobiology of Proprioceptive Regulation of Bone and Joint Morphogenesis

Projektinformationen

BONE-JOINT-MORPH

ID Finanzhilfevereinbarung: 798248

DOI

10.3030/798248

Projekt abgeschlossen

EK-Unterschriftsdatum 17 Juli 2018

Startdatum 1 September 2018

Enddatum 31 August 2020

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 183 454,80

EU-Beitrag

€ 183 454,80

Koordiniert durch

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom

Periodic Reporting for period 1 - BONE-JOINT-MORPH (Mechanobiology of Proprioceptive Regulation of Bone and Joint Morphogenesis)

Berichtszeitraum: 2018-09-01 bis 2020-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Physiological movement, including movement before birth (fetal movement), is necessary for maintaining a proper mechanical environment which will facilitate musculoskeletal development. Developmental dysplasia of the hip (DDH) is a condition which can result due to abnormal loading either before or after birth. With DDH, the acetabular socket is often shallow causing an improper fit of the femoral head within the socket, leading to hip instability or even dislocation6. DDH is the most commonly abnormal joint in new-born babies, with an incidence of 4.9 out of 100012. However, it is not known why the hip, more than any other joint in the body, is so dependent on movements and mechanical stimulation for its normal development. Recent studies on the proprioceptive system (the neuromuscular sensory receptors responsible for registering position and movement of body parts) have indicated a key role in skeletogenesis. Disruption of the proprioceptive system in mice through knocking out Runt-related transcription factor 3 (RUNX3 KO has been found to cause gait ataxia, spinal scoliosis and fracture misalignment. Excitingly, unpublished data from the same animal model has indicated that hip dysplasia consistently occurs in these mice (Fig. 1), with all other synovial joints forming normally. It is hypothesised that the hip joint abnormalities arise as a direct effect of the abnormal mechanical environment due to abnormal gait. Therefore, this model system offers a unique opportunity to reveal how movement shapes the developing joint, and in particular, why the hip joint is more dependent on normal movements than any other joint. Therefore, this project will potentially reveal new insights into the causes and aetiology of DDH.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The musculoskeletal modelling framework was established.
The walkway for mouse gait recording was designed and developed.
The protocol to record the gait of the healthy and mutant mouse was established.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The project was terminated before the scheduled end date as I received a permanent job in academia elsewhere. However, I am still in touch with my mentors and we are planning to take the project forward through suitable external funding.

Testing set-up